PXD060639

PXD060639 is an original dataset announced via ProteomeXchange.

Title	Quieting the Storm: Hypoxia as a Strategy to Boost UC-MSC Therapies for Hypoxic-Ischemic Brain Lesions in Neonatal Rats
Description	Integrating stem cell therapies into clinical settings faces several challenges, particularly in achieving the high cell yields necessary for attaining therapeutic doses. Preconditioning with hypoxic conditions has shown promise in enhancing the mesenchymal stem cells (MSCs)’ reparative capabilities of the central nervous system. Recent evidence suggests that oxygen concentration and exposure duration can shape MSCs’ phenotypes, supporting the need for further optimization of this strategy in a way to achieve maximal repair. Methods: Wistar Han rat pups from both sexes underwent hypoxic-ischemic (HIE) brain injury at postnatal day 10 using the Rice-Vannucci model and were treated with umbilical cord derived-MSCs (UC-MSCs) preconditioned with prolonged mild hypoxia (MH; 5% oxygen for 48 hours) or short severe hypoxia (SSH; 0.1% oxygen for 24 hours) two days later. Results: Our results show that UC-MSCs’ were able to alleviate motor and cognitive deficits caused by the HI brain lesion. To investigate the molecular effects of hypoxia-preconditioned MSCs in the neonatal brain post-HIE, we employed untargeted proteomics on ipsilesional brain samples from control, HIE, HIE treated with naïve UC-MSCs, and HIE treated with SSH-preconditioned UC-MSCs groups, 30 days after lesion induction. This approach identified protein signatures related to injury and therapeutic intervention. Pathway enrichment analysis further revealed that administration of UC-MSCs preconditioned with short severe hypoxia significantly impacted neural signaling, protein synthesis, and energy metabolism pathways, pointing to long-term mechanisms that may support neuronal repair. Conclusion: These findings enhance our understanding of hypoxia-preconditioning in MSCs therapy in driving a positive therapeutic response, supporting the development of more effective and feasible treatments for neonatal hypoxic-ischemic brain injury.
HostingRepository	PRIDE
AnnounceDate	2026-04-27
AnnouncementXML	Submission_2026-04-26_20:19:46.356.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vera Mendes
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: NEWT:10116;
ModificationList	S-carboxamidoethyl-L-cysteine
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-10 08:39:25	ID requested
⏵ 1	2026-04-26 20:19:47	announced

10.1007/s12015-026-11089-6;

Serrenho I, Mendes V, Caramelo I, Cardoso CMP, Manadas B, Baltazar G, Quieting the Storm: Hypoxia as a Strategy to Boost UC-MSC Therapies for Hypoxic-Ischemic Brain Lesions in Neonatal Rats. Stem Cell Rev Rep, 22(4):1974-2000(2026) [pubmed]

submitter keyword: Mesenchymal stem cell

Brain hypoxia

Cell therapy

Hypoxic ischemic encephalopathy

Preconditioning

Proteomics

Graça Baltazar
contact affiliation	Faculty of Health Sciences, University of Beira Interior, Covilhã
contact email	gbaltazar@fcsaude.ubi.pt
lab head
Vera Mendes
contact affiliation	Center for Neuroscience and Cell Biology, University of Coimbra
contact email	vera3m@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060639
     1. Label: PRIDE project
     2. Name: Quieting the Storm: Hypoxia as a Strategy to Boost UC-MSC Therapies for Hypoxic-Ischemic Brain Lesions in Neonatal Rats